Interactions between insulin, body fat, and insulin-like growth factor axis proteins

The etiology of hormonally related cancers, such as breast and colon, has been linked to hyperinsulinemia and insulin resistance, the insulin-like growth factor (IGF) axis, and obesity.

Data from 57 women (ages 30-50 years) were used to observationally examine cross-sectional and longitudinal relations between body fat (from dual-energy X-ray absorptiometry), insulin, IGF-I, and IGF-binding proteins (IGFBP-1, IGFBP-2, and IGFBP-3).

At baseline, participants who had greater than median body fat and insulin levels, >39% and >4.5 microunits/mL, respectively, had 2.3- to 2.6-fold lower IGFBP-1 (P < 0.004) and 1.9- to 2.0-fold lower IGFBP-2 (P < 0.004) compared with other participants; IGF-I and IGFBP-3 levels did not differ by body fat or insulin levels. Over 39 weeks, a 1 microunit/mL reduction in fasting insulin was associated with a 17% increase in IGFBP-1 (P = 0.02) and a 24% increase in IGFBP-2 (P = 0.02) compared with participants who did not reduce insulin; 2.0% loss of body fat over time did not alter IGFBP-1 or IGFBP-2 levels after adjustment for insulin. IGF-I and IGFBP-3 did not change in participants who lost body fat percentage or insulin over time.

These observational associations are consistent with the hypothesis that elevated insulin and body fat are associated with decreased IGFBP-1 and IGFBP-2 levels cross-sectionally; they further imply that IGFBP-1 and IGFBP-2 levels may be altered through change in insulin over time. By contrast, no cross-sectional or longitudinal associations were noted between IGF-I and IGFBP-3 with insulin or body fat.